Highlights from the European Hematology Association Congress 2025

The treatment of multiple myeloma developed and remarkably improved over the last decade. Still there is a medical need for efficient and safe therapies. This year’s congress of the European Hematology Association (EHA) provided insights to upcoming treatment options for patients with newly diagnosed and relapsed or refractory multiple myeloma (RRMM). Herein we report some of the novel strategies.The Italian FORTE-trial randomized 474 newly diagnosed, transplant-eligible patients younger than 65 years from 42 Italian centers comparing carfilzomib-lenalidomide-dexamethasone (KRd) induction plus autologous stem cell transplant (KRd-ASCT) versus KRd induction plus KRd consolidation (KRd12) versus carfilzomib-cyclophosphamide-dexamethasone (KCd) induction plus ASCT (KCd-ASCT). Thereafter patients of the 3 study arms were randomized into one of 2 maintenance arms with KR versus R. With a median follow-up of 93.6 months the median PFS of the induction and consolidation phase in the KRd-ASCT arm was 99 months, thus significantly longer than in the KRd arm with a median 70 months (HR 0.69; p = 0.019) and the KCd-ASCT arm with a median 64 months (HR 0.63; p = 0.003) [1]. The median time to next treatment was not reached at 8 years with KRd-ASCT, thus significantly longer compared to KRd12 with a median of 70 months (HR 0.55; p < 0.001) and KCd-ASCT with a median of 6.5 months (HR 0.60; p = 0.003). The 8-year overall survival (OS) rate was similar in the 3 treatment arms with 75% versus 73% (HR 0.82; p = 0.370) versus 68% (HR 0.65; p = 0.050). Median follow-up from the second randomization was 83.9 months. Despite stopping carfilzomib after 2 years and continuing with lenalidomide alone in both arms, there was a significant PFS benefit of KR versus R (HR 0.70; p = 0.040). The Kaplan-Meier curves separated for up to 4 years from randomization and approached each other over time. Seven years after the second randomization the PFS rate was 73% (HR 1.07; p = 0.736) versus 68%, and the OS rate 82% versus 76% (HR 1.03; p = 0.907).Myeloma patients with extramedullary disease (EMD) have poor outcomes with standard therapies. Heavily pretreated triple-class exposed RRMM with and without EMD from the LocoMMotion and MoMMent studies reached a median PFS of 2.7 and 5.1 months, and a median OS of 7.2 and 15.5 months, respectively. A total of 24.1% and 33.3% of the patients responded to a standard therapy [2]. Anti-GPRC5D/CD3 bispecific antibody talquetamab and anti-BCMA/CD3 bispecific antibody teclistamab are approved as monotherapies for triple-class exposed RRMM. The phase 2 study RedircTT-1 examined the combination of talquetamab (0.8 mg/kg, q2w sc) and teclistamab (3.0 mg/kg, q2w sc) for RRMM patients with EMD [3]. Ninety patients received talquetamab plus teclistamab. The median age was 64.5 years, 22% of the patients had high-risk cytogenetics, and the median number of prior lines of therapy was 4.0 with a range from 1 to 10. Overall, 20% of the patients had been treated with an anti-BCMA CAR-T therapy, 84% were triple-class refractory, and 36% were penta-drug refractory. The objective response rate (ORR) was 78.9%, and 54.4% of patients received at least a complete response (≥CR). In total, 83.3% of patients with prior anti-BCMA CAR-T therapy had an ORR, while 66.2% of the responders remained on therapy with a median follow-up of 13.4 months. The median PFS was 15.4 months. After 1 year the PFS rate was 61.0%, and the OS rate was 74.5%. The safety was consistent with the known profiles of talquetamab and teclistamab. The rates of severe infections were similar to the monotherapies, underscoring the importance of vigilant infection prophylaxis and management.Another strategy for patients with RRMM is treatment with a novel, next-generation trispecific antibody [4]. JNJ-5322 binds to BCMA, GPRC5D, and CD3. Results of an initial phase 1 trial show promising results for heavily pretreated all triple-class and often penta-class exposed patients. Half of the patients were triple-class refractory and 94.4% refractory to their last line of therapy. All 27 BCMA/GPRC5D-naive patients receiving 100 mg (q4w, sc) of JNJ-5322 responded to the study treatment. Almost all patients remained in response with 12 months of follow-up. With a manageable safety and an ORR comparable to a CAR-T therapy, JNJ-5322 is a convenient, off-the-shelf therapy. Dosing every 4 weeks with only 1 step-up dosing facilitates outpatient treatment.In summary, for newly diagnosed myeloma patients a carfilzomib-based regimen seems to be an effective treatment option. Heavily pretreated patients may benefit from the combination of two bispecific antibodies or the treatment with a trispecific antibody.The author has no conflicts of interest to declare.Karger Publishers provided financial support for the preparation of this article by a medical writer. Karger had a role in the manuscript conception. Karger had no role in the manuscript writing and decision to publish. Decisions regarding the content of the resource rest with the named author.Ine Schmale is the sole author of this article.